Angiogenesis in triple-negative adenoid cystic carcinomas of the breast

We compared microvascular density (MVD), lymph vessel density (LVD), and the expression of hypoxia pathway-associated proteins between primary triple-negative adenoid cystic carcinoma of the breast (TN-ACC) and grade-matched triple-negative breast carcinomas of no special type (TNBC). Twelve TN-ACC and 15 TNBC were investigated immunohistochemically for CD31, podoplanin (D2-40), von Hippel-Lindau protein (pVHL), and hypoxia-inducible factor-1alpha (HIF-1α) protein. All cases were lymph node negative (pN0). The study revealed a median MVD (CD31) of 34 vessels/mm(2) (mean ± SD, 41.33 ± 6.5/mm(2)) in the TN-ACC subgroup and a median of 55 microvessels (mean ± SD, 54.9 ± 6.3/mm(2)) in the TNBC subgroup. The median LVD (D2-40) was 10.5/mm(2) (mean ± SD, 11.9 ± 1.5/mm(2)) in the TN-ACC subgroup and 15.0/mm(2) (mean ± SD, 16.9 ± 2.5/mm(2)) lymph vessels in the TNBC subgroup. The differences were not statistically significant (P = 0.93, P = 0.67, respectively). pVHL was detectable in all TN-ACCs whereas two cases of TNBC had less than 5% of the positive cells. HIF-1α protein expression was significantly higher in the tumor cell population than in adjacent normal cells in both subgroups (P = 0.009 for TNBC and P = 0.028 for TN-ACC, respectively), but there was no significant difference between the two tumor groups. Up-regulation of the hypoxia-induced signaling is seen in both TN-ACC and grade-matched TNBC. Despite its perceived low malignant potential, TN-ACC of the breast does not differ in the number of blood and lymphatic vessels in comparison with the grade-matched TNBC. The reported biologic differences between TN-ACC and TNBC do not appear to result from neoangiogenesis.